The administration of drugs and other biological materials to the bloodstream via a transdermal route or to the localized site of action has received much attention in recent years. The skin of an average adult covers generally more than two square meters of surface area and receives about one third of all blood circulating through the body. It is elastic, rugged, and generally self-generating. The skin consists of three layers: the stratum corneum, the epidermis, and the dermis.
The stratum corneum represents the rate limiting step in diffusion of chemicals through the skin. The stratum corneum is composed of dead, keratinized, metabolically inactive cells, which are closely packed together, and consists of an amorphous matrix of mainly lipoid and non fibrous protein within which keratin filaments are distributed. The cells of the stratum corneum generally contain about 20% water, while the cells below, in the stratum germinivatum contain about 70% water. The stratum corneum does not become hydrated readily. Thus, transdermal permeation is primarily controlled by diffusion through the stratum corneum.
Due to availability of large surface area, easy accessibility, application dynamics and the noninvasive nature of the therapy, topical administration of drugs has long been considered a promising route of drug delivery whether the bioavailability desired is systemic, dermal, regional or localized. The topical mode of drug delivery provides many advantages over customarily used routes of administration. First, it bypasses the portal circulation and thereby the hepatic first pass metabolism. Second, topical delivery avoids the problems of variable systemic absorption and metabolism. Third, it potentially reduces gastrointestinal irritation associated with oral administration. Further, it avoids the risks and patient noncompliance associated with parenteral treatment.
The topical delivery route offers continuity of drug administration, permits use of therapeutic agents with short biological half-lives, provides treatment of cutaneous manifestations of diseases usually treated systemically, delivers medication directly into the systemic circulation, and fosters ease of use and total patient compliance.
Ointments are semisolid preparations intended for external application to the skin or mucous membranes. Ointments may be medicated or non-medicated. Non-medicated ointments are ordinarily used for the physical effects that they provide as protectants, emollients or lubricants. Medicated ointments include an active pharmaceutical ingredient (API). Ointments include an ointment base component, such as petrolatum.
Petrolatum based topical compositions possess occlusive and emollient properties and are often used in for the delivery of active agents. However, because of the viscous and lipophilic nature of petrolatum, the release of active agents from petrolatum based compositions is generally slow and can hinder therapeutic efficacy. Slow delivery can be a particular problem when the composition includes an active agent that is water-miscible or hydrophilic. For example, petrolatum based compositions are desirable for treatment of bacterial, fungal infection, and wound healing applications where an occlusive layer formed by petrolatum is highly desirable. However, many agents that have anti-bacterial, anti-fungal, and wound-healing activities are water-miscible or hydrophilic and may not release efficiently through the petrolatum. Efficacies of the dosage forms are believed to be directly related to amount of the active agents being released from the dosage forms to targeted tissues, such as, for example, skin, ocular, or nasal tissues. Release of the active agents from the petrolatum based compositions is thought to be through diffusion of the agents from within the compositions to surface of the compositions. For compositions intended to treat bacterial, fungal infection, or for wound healing, enhanced release of the active agents generally corresponds to enhanced therapeutic efficacy. In addition, enhanced release of the active agents might also lead to enhanced delivery to various animal or human tissues, such as, skin, ocular, nasal, for example, when the compositions are applied topically to surfaces of the tissues.
There is a need for release enhancing agents to increase release of active agents from petrolatum based compositions. There is also a need for topical compositions with enhanced therapeutic efficacy.